Investigation characteristics of polyvinyl alcohol film dyed methylene blue and irradiated by gamma source

Journal of Radioanalytical and Nuclear Chemistry - The polyvinyl alcohol (PVA) films dyed methylene blue containing different masses of boric acid and PVA powder were investigated. The dyed PVA...     

Poisson Statistics for Beta Ensembles on the Real Line at High Temperature

Journal of Statistical Physics - This paper studies beta ensembles on the real line in a high temperature regime, that is, the regime where $$beta N rightarrow const in (0, infty )$$, with N...     

Synthesis of Nitro-Aryl Functionalised 4-Amino-1,8-Naphthalimides and Their Evaluation as Fluorescent Hypoxia Sensors

Fluorescent sensors are a vital research tool, enabling the study of intricate cellular processes in a sensitive manner. The design and synthesis of responsive and targeted probes is necessary to allow such processes to be interrogated in the cellular environment. This remains a challenge, and requires methods for functionalisation of fluorophores with multiple appendages for sensing and targeting groups. Methods to synthesise more structurally complex derivatives of fluorophores will expand their potential scope. Most known 4-amino-1,8-naphthalimides are only functionalised at imide and 4-positions, and structural modifications at additional positions will increase the breadth of their utility as responsive sensors. In this work, methods for the incorporation of a hypoxia sensing group to 4-amino-1,8-naphthalimide were evaluated. An intermediate was developed that allowed us to incorporate a sensing group, targeting group, and ICT donor to the naphthalimide core in a modular fashion. Synthetic strategies for attaching the hypoxia sensing group and how they affected the fluorescence of the naphthalimide were evaluated by photophysical characterisation and time-dependent density functional theory. An extracellular hypoxia probe was then rationally designed that could selectively image the hypoxic and necrotic region of tumour spheroids. Our results demonstrate the versatility of the naphthalimide scaffold and expand its utility. This approach to probe design will enable the flexible, efficient generation of selective, targeted fluorescent sensors for various biological purposes.     

Unifying the steady state resonant solutions of the periodically forced KdVB, mKdVB, and eKdVB equations

The periodically forced extended KdVB (eKdVB) equation, which contains both KdVB and modified KdVB (mKdVB) equations as special cases, is known to possess a rich array of resonant steady solutions. We present an analytic methodology based on singular perturbation and asymptotic matching in order to illustrate and approximate these solutions in the limit that the dispersive effects are small relative to the nonlinear and forcing terms. Weak Burgers damping is also included at the same order as dispersion. Solutions across the resonant band may be constructed and show good agreement with solutions of the full equation, showing clearly the role of the various physical effects. In this way, direct comparisons and connections are made between the various classes of KdVB equations, illustrating, in particular, the underlying mathematical connections between the KdVB and mKdVB equations.     

On contraction of nonlinear difference equations with time‐varying delays

General nonlinear difference equations with time‐varying delays are considered. Explicit criteria for contraction of such equations are presented. Then some simple sufficient conditions for global exponential stability of equilibria and for stability of invariant sets are derived. Furthermore, explicit criteria for existence, uniqueness and global exponential stability of periodic solutions are derived. Finally, the obtained results are applied to time‐varying discrete‐time neural networks with delay.     

Pileamartines A and B: Alkaloids from Pilea aff. martinii with a new carbon skeleton

Two novel alkaloids, with an unprecedented carbon skeleton, pileamartines A (1) and B (2), together with the known alkaloid, julandine (I-a) were isolated from the alkaloidal fraction of Pilea aff. martinii leaves. Their structures were established by spectral data analysis, including MS and 2D NMR. The absolute configurations of 1 and 2 were suggested by comparison of their experimental and calculated electronic circular dichroism spectra. Compound 2 exhibited weak inhibitory activity against the α-glucosidase enzyme with an inhibition of 11% at a concentration of 200?µM. These compounds were not cytotoxic against several cancer cell lines even at a concentration of 150?µM.     

Identification of β-strand mediated protein–protein interaction inhibitors using ligand-directed fragment ligation

β-Strand mediated protein–protein interactions (PPIs) represent underexploited targets for chemical probe development despite representing a significant proportion of known and therapeutically relevant PPI targets. β-Strand mimicry is challenging given that both amino acid side-chains and backbone hydrogen-bonds are typically required for molecular recognition, yet these are oriented along perpendicular vectors. This paper describes an alternative approach, using GKAP/SHANK1 PDZ as a model and dynamic ligation screening to identify small-molecule replacements for tranches of peptide sequence. A peptide truncation of GKAP functionalized at the N- and C-termini with acylhydrazone groups was used as an anchor. Reversible acylhydrazone bond exchange with a library of aldehyde fragments in the presence of the protein as template and in situ screening using a fluorescence anisotropy (FA) assay identified peptide hybrid hits with comparable affinity to the GKAP peptide binding sequence. Identified hits were validated using FA, ITC, NMR and X-ray crystallography to confirm selective inhibition of the target PDZ-mediated PPI and mode of binding. These analyses together with molecular dynamics simulations demonstrated the ligands make transient interactions with an unoccupied basic patch through electrostatic interactions, establishing proof-of-concept that this unbiased approach to ligand discovery represents a powerful addition to the armory of tools that can be used to identify PPI modulators.

Dynamic ligation screening is used to identify acylhydrazone-linked peptide-fragment hybrids which bind to the SHANK1 PDZ domain with comparable affinity to the native GKAP peptide as shown by biophysical and structural analyses.     

Amplified Self-Immolative Release of Small Molecules by Spatial Isolation of Reactive Groups on DNA-Minimal Architectures

Triggering the release of small molecules in response to unique biomarkers is important for applications in drug delivery and biodetection. Due to low quantities of biomarker, amplifying release is necessary to gain appreciable responses. Nucleic acids have been used for both their biomarker-recognition properties and as stimuli, notably in amplified small-molecule release by nucleic-acid-templated catalysis (NATC). The multiple components and reversibility of NATC, however, make it difficult to apply in vivo. Herein, we report the use of the hybridization chain reaction (HCR) for the amplified, conditional release of small molecules from standalone nanodevices. We couple HCR with a DNA-templated reaction resulting in the amplified, immolative release of small molecules. We integrate the HCR components into single nanodevices as DNA tracks and spherical nucleic acids, spatially isolating reactive groups until triggering. This could be applied to biosensing, imaging, and drug delivery.     

Oxidized Xanthan Gum Crosslinked NOCC: Hydrogel System and Their Biological Stability from Oxidation Levels of the Polymer

Dynamic hydrogel systems from N,O-carboxymethyl chitosan (NOCC) are investigated in the past years, which has facilitated their widespread use in many biomedical engineering applications. However, the influence of the polymer's oxidation levels on the hydrogel biological properties is not fully investigated. In this study, chitosan is converted into NOCC and introduced to react spontaneously with oxidized xanthan gum (OXG) to form several injectable hydrogels with controlled degradability. Different oxidation levels of xanthan gum, as well as NOCC/OXG volume ratios, are trialed. The infrared spectroscopy spectra verify chemical modification on OXG and successful crosslinking. With increasing oxidation levels, more dialdehyde groups are introduced into the OXG, resulting in changes in physical properties including gelation, swelling, and self-healing efficiency. Under different volume ratios, the hydrogel shows a stable structure and rigidity with higher mechanical properties, and a slower degradation rate. The shear-thinning and self-healing properties of the hydrogels are confirmed. In vitro assays with L929 cells show the biocompatibility of all formulations although the use of a high amount of OXG15 and OXG25 limited the cell proliferation capacity. Findings in this study suggested a suitable amount of OXG at different oxidation levels in NOCC hydrogel systems for tissue engineering applications.     

Preparation of Information‐Containing Macromolecules by Ligation of Dyad‐Encoded Oligomers

A simplified strategy for preparing non‐natural information‐containing polymers is reported. The concept relies on the successive ligation of oligomers that contain minimal sequence motifs. It was applied here to the synthesis of digitally‐encoded poly(triazole amide)s, in which propyl and 2‐methyl propyl motifs are used to code 0 and 1, respectively. A library of four oligo(triazole amide)s containing the information dyads 00, 01, 10, and 11 was prepared. These oligomers contain two reactive functions, that is, an alkyne and a carboxylic acid. Thus, they can be linked to another with the help of a reactive spacer containing azide and amine functions. Using two successive chemoselective steps, that is, azide‐alkyne Huisgen cycloaddition and carboxylic acid‐amine coupling, monodisperse polymers can be obtained. In particular, the library of dyads permits the implementation of any desired sequence using a small number of steps. As a proof‐of‐concept, the synthesis of molecular bytes 00000000 and 00000110 is described.